B CELL STIMULATORY FACTOR-1 (BSF-1)/INTERLEUKIN-4

B 细胞刺激因子-1 (BSF-1)/白细胞介素-4

• 批准号: 3803202
• 负责人: W E PAUL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3803202
• 关键词: B lymphocyte; T cell receptor; T lymphocyte; active immunization; antiantibody; antibody formation; biological signal transduction; bone marrow; crosslink; cytochrome c; gene rearrangement; genetically modified animals; immunoglobulin E; immunoglobulin genes; immunoregulation; interleukin 3; interleukin 4; laboratory mouse; leukocyte activation /transformation; mast cell; phosphorylation; tissue /cell culture

Interleukin-4 (IL-4) is a potent lymphokine that mediates a wide variety of functions on both hematopoietic and non-hematopoietic cells. Both in vivo and in vitro, it controls the production of IgE antibodies by regulating the process through which B cells switch to the expression of immunoglobulin of that isotype. Among T cells from naive donors, very few (about 1/1000) are capable of producing IL-4 in response to a polyconal stimulant such as immobilized anti-CD3 antibody. Immunization of mice in such a way as to induce high levels of IgE, such as infection with parasitic nematodes or injection of anti-IgD antibody, results in the appearance of large numbers of T cells that can produce IL-4. In vitro priming systems bave been developed through which T cells can develop into IL-4 producing cells. These systems depend upon the action of IL-4 itself on precursors of IL-4-producing cells. Such priming can be achieved both by polyclonal stimulants and, using mice transgenic for a T cell receptor specific for cytochrome c, by antigen-specific stimulation. IL-4 is also produced by FcepsilonRI+ cells in response to cross-linkage of FCepsilonRI, of FcgammaRIII or to treatment with ionomycin. In bone marrow cell cultures grown for 5-7 days with IL-3, the principal IL-4 producing cell is FcepsilonRI+, c-kit-. Upon isolation, such cells are strikingly enriched in basophils, strongly suggesting that this cell is the predominant hematopoietic cell, other than the T cell, that produces IL-4 in responses to a receptor-mediated stimulation. The capacity of such cells to produce IL-4 is markedly augmented by treatment with IL-3. Current evidence suggests that IL-3 functions by increasing the strength of the signal generated by cross-linkage of FcepsilonRI, as shown by increase in tyrosine phosphorylation of certain substrates in response to FcepsilonRI cross-linkage in mast cells that had been precultured in IL-3.

白介素-4（IL-4）是一种有效的淋巴动物，可介导多种 在造血和非山大麻细胞上的功能。两者都在 体内和体外，它可以控制IgE抗体的产生 调节B细胞切换到表达的过程 该同种型的免疫球蛋白。 在天真供体的T细胞中，非常 很少有（约1/1000）能够响应于A 多结构刺激剂，例如固定的抗CD3抗体。 免疫 诱导高水平的IgE的方式，例如感染 用寄生线虫或注射抗IGD抗体，导致 可以产生IL-4的大量T细胞的出现。 在 体外启动系统开发了通过T细胞可以通过该系统 发展成IL-4产生的细胞。这些系统取决于动作 IL-4本身在产生IL-4的细胞的前体上。 这样的启动可以 可以通过多克隆兴奋剂和使用小鼠转基因来实现 通过抗原特异性的T细胞受体对细胞色素c的特异性受体 刺激。 Fcepsilonri+细胞还会生产IL-4，以响应交叉链接 fcepsilonri，fcgammariii或用离子霉素治疗。 在骨头 用IL-3（主要IL-4）生长5-7天的骨髓细胞培养物 产生的细胞是fcepsilonri+，c-kit-。 隔离后，这样的细胞是 在嗜碱性粒细胞中非常富集，强烈表明该细胞是 除T细胞以外的主要造血细胞，它会产生 IL-4在对受体介导的刺激的反应中。 能力 通过用IL-3处理可以显着增强这种产生IL-4的细胞。 当前的证据表明，IL-3通过提高强度发挥作用 fcepsilonri的交联产生的信号，如 响应某些底物的酪氨酸磷酸化增加 在已在 IL-3。